The present invention is concerned with a process for the manufacture of .beta.-ionone from pseudoionone in a two-phase solvent system.
Many important industrial syntheses are carried out in heterogeneous liquid/liquid (two-phase) solvent systems, with the reaction taking place either directly at the phase boundary or in the bulk phase of the extractant.
Industrial examples of reactive heterogeneous liquid/liquid solvent systems are found, inter alia, in important intermediate stages in the synthesis of vitamin A. Here, reactants and products are distributed between two liquid phases.
Nowadays industrial syntheses are also systematically modified when they are in competition with existing and optimized production processes. In particular, the increased importance of product- and production-integrated environmental protection can mostly not be satisfied by new plant and equipment alone. Rather, changing the material system, if this is possible, frequently offers a much greater potential. The physiological concerns and the ecological problems connected with the chlorinated organic solvents used in the industrial process for the synthesis of vitamin A provide the motivation for development of an alternative process concept. In the industrial process, efforts are also made for economical and also ecological reasons to reduce the amount of sulphuric acid used, and thus reduce the environmentally problematic dilute acid obtained in the process, and such endeavours likewise provide a motivation.
The objective of the industrial synthesis of vitamin A is to build up the vitamin A structure with its 20 carbon atoms from readily available components, e.g., from petrochemicals. In .beta.-ionone, a cyclic terpene ketone [4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-buten-2-one], there is already available a molecule which contains 13 carbon atoms including the terminal C.sub.6 ring in the configuration corresponding to vitamin A. All large-scale processes for the synthesis of vitamin A therefore proceed via .beta.-ionone as an intermediate.
The Isler synthesis (Roche) of 1948, the key step of which is based on the linking of a C.sub.14 component formed from .beta.-ionone with a C.sub.6 component, can be regarded up to now as one of the most economically successful processes for the total synthesis of vitamin A. In its industrial implementation, this synthesis comprises 11 stages, of which the second consists of the cyclization of pseudoionone to .beta.-ionone in the presence of sulphuric acid. .beta.-ionone is converted via the glycidic ester synthesis into the C.sub.14 component, 2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-buten-1-al (the "C.sub.14 aldehyde"), which in turn is linked, via a Grignard reaction, with the C.sub.6 component, 3-methyl-pent-2-en-4-yn-1-ol, synthesized in three reaction steps. Vitamin A acetate is obtained in crude form from the resulting oxenyne after partial Lindlar hydrogenation, acetylation with acetic anhydride, dehydration and rearrangement. After purification by crystallization and trans-esterification with methyl palmitate, vitamin A palmirate is formed, the commercial end product of the large-scale synthesis.
The central compound of all vitamin A syntheses is .beta.-ionone, which can be obtained from pseudoionone (6,10-dimethylundeca-3,5,9-trien-2-one) by a ring-closure reaction under the action of strong protonic acids. In this ring-closure reaction, there also simultaneously results .alpha.-ionone [4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one] which differs from the isomeric .beta.-ionone only by the position of the double bond in the ring with the formation of an asymmetric carbon atom having the (R) configuration. .alpha.-ionone is principally used in the perfume industry as an odorant precursor.
The use of chlorinated hydrocarbons as solvents in organic syntheses is widespread. The exceptional solvent power of methylene chloride, not only for terpenoid compounds but also for a majority of the polymeric byproducts formed in the synthesis, is the basis for its use in industrial vitamin A production. In addition, the high density of methylene chloride favours dispersion of the sulphuric acid during the cyclization of pseudoionone, which permits a high mass transfer rate in the two-phase system. At the same time, however, the subsequent separation of the sulphuric acid phase is made more difficult. As already indicated above, the use of chlorinated solvents such as, for example, methylene chloride, is more and more the subject of ecological debate. Despite reprocessing of the solvent, leakage losses in industrial plants are unavoidable in view of the high vapour pressure of methylene chloride. Chlorinated hydrocarbons which are released are suspected of being capable of causing changes in the constitution of the atmosphere. In addition, these solvents are considered to have a carcinogenic action, so that their use in the production of pharmaceutical products and foodstuffs is questionable, not least from a psychological point of view. Despite the advantages which chlorinated hydrocarbons offer in industrial production, for these reasons there is an intensive search for replacement by alternative solvents and processes.
In the industrial-scale plant, pseudoionone is continuously reacted completely with highly concentrated, e.g., 98%, sulphuric acid, with .beta.-ionone being obtained in a yield of about 90%. The pseudoionone is taken from intermediate storage tanks via metering pumps and is dissolved in methylene chloride. The thus-diluted educt, pseudoionone, is mixed intensively in the reaction zone with sulphuric acid in a weight ratio of about 1:2 (educt:acid). The acid is soluble in methylene chloride to only a small extent, so that a two-phase liquid/liquid system forms in which the reaction is initiated at the phase boundary. The pseudoionone educt reacts at the surface of the dispersed sulphuric acid droplets. The products formed remain bound in the acid phase. The heat liberated in the strongly exothermic reaction is removed by pre-cooling the pseudoionone/methylene chloride stream and intensively cooling in the reactor to maintain a temperature of 0.degree. to 5.degree. C., especially about 0.degree. C. Since .beta.-ionone in contact with sulphuric acid forms high molecular weight, polymeric byproducts with increasing reaction time, it is necessary to suppress further reaction. In a so-called quenching stage, the sulphuric acid is diluted by the metered addition of water to a sufficient extent, normally to an about 18% aqueous solution, so that with simultaneous separation of the resulting organic and the acidic aqueous phase the reaction is stopped. The liberated enthalpy of dilution must be removed in this case. Since it is also extremely desirable, for economical and ecological reasons, to feed the sulphuric acid back into the reaction system for re-use, the strongly diluted aqueous sulphuric acid solution must be purified and concentrated, which because of the required degree of concentration (from about 18% up to about 98%) is very energy-intensive and costly.